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The efficiency of insulin production and its content in insulin-expressing model β-cells correlate with their Zn 2+ levels: Zn 2+ levels in β-cells

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Author(s)

  • Petra Dzianová
  • Seiya Asai
  • Martina Chrudinová
  • Lucie Kosinová
  • Pavlo Potalitsyn
  • Pavel Šácha
  • Romana Hadravová
  • Irena Selicharová
  • Jan Kříž
  • Johan P. Turkenburg
  • Andrzej Marek Brzozowski
  • Jiří Jiráček
  • Lenka Žáková

Department/unit(s)

Publication details

JournalOpen Biology
DateAccepted/In press - 24 Sep 2020
DatePublished (current) - 21 Oct 2020
Issue number10
Volume10
Number of pages13
Original languageEnglish

Abstract

Insulin is produced and stored inside the pancreatic β-cell secretory granules, where it is assumed to form Zn 2+ -stabilized oligomers. However, the actual storage forms of this hormone and the impact of zinc ions on insulin production in vivo are not known. Our initial X-ray fluorescence experiment on granules from native Langerhans islets and insulinoma-derived INS-1E cells revealed a considerable difference in the zinc content. This led our further investigation to evaluate the impact of the intra-granular Zn 2+ levels on the production and storage of insulin in different model β-cells. Here, we systematically compared zinc and insulin contents in the permanent INS-1E and BRIN-BD11 β-cells and in the native rat pancreatic islets by flow cytometry, confocal microscopy, immunoblotting, specific messenger RNA (mRNA) and total insulin analysis. These studies revealed an impaired insulin production in the permanent β-cell lines with the diminished intracellular zinc content. The drop in insulin and Zn 2+ levels was paralleled by a lower expression of ZnT8 zinc transporter mRNA and hampered proinsulin processing/folding in both permanent cell lines. To summarize, we showed that the disruption of zinc homeostasis in the model β-cells correlated with their impaired insulin and ZnT8 production. This indicates a need for in-depth fundamental research about the role of zinc in insulin production and storage.

Bibliographical note

© 2020 The Authors

    Research areas

  • insulin, pancreatic islets, proinsulin, zinc ions, znt8, β-cells

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